{
  "abstract": "Acute pancreatitis (AP) is an acute inflammatory disorder of the exocrine pancreas with limited therapies. Whether cuproptosis, a copper-dependent cell death pathway, contributes to AP pathogenesis remains unknown. We integrated single-cell transcriptomics (GSE279876), single-cell transcriptomics (GSE188819), and human whole-blood transcriptomic data (GSE194331) to evaluate 13 cuproptosis-related genes across cell types, along with pseudotime trajectory, regulatory networks, and cell–cell communication. Findings were validated in caerulein-induced severe acute pancreatitis (SAP) mouse models and acinar cell injury using histopathology, electron microscopy, flow cytometry, immunofluorescence, and biochemical assays. Single-cell analysis showed selective activation of a cuproptosis-related signature in acinar cells, with all 13 genes upregulated, most notably GIs and Fdx1. The cuproptosis-related gene signature score increased along with pseudotime, and exploratory transcription factor (TF) and cell–cell communication analyses suggested enrichment of SPI1 and AP-1 (FOS/JUN), alongside MIF/CCL inflammatory signals, which was corroborated in independent datasets. In vitro and in vivo, pancreatic tissues and pancreatic acinar cells in SAP exhibited copper accumulation, FDX1/DLAT upregulation, mitochondrial shrinkage, and cristae loss, which are consistent with a cuproptosis-related phenotype, and were all attenuated by Tetrathiomolybdate (TTM). These findings suggest that the inflammatory microenvironment may be associated with selective activation of a cuproptosis-related program in acinar cells in AP, and that copper chelation with TTM attenuates pancreatic injury, indicating a potential therapeutic strategy targeting copper dyshomeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China",
    "Institute of Animal Nutrition and Feed Sciences, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qingfeng Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Maoqin He"
    },
    {
      "affs": [
        1
      ],
      "name": "Qi Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiqin Li",
      "orcid": "0000-0002-8483-6264"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3z6w06pgpdfse.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209004",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705439/?tool=EBI",
  "id": "3z6w06pgpdfse",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9004",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2746|Pancreatitis Pathology and Treatment"
    ]
  ],
  "openalex": "W7212217725",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705439/pdf/?tool=EBI",
  "pmcid": "PMC13705439",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3z6w06pgpdfse.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27209004",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9004"
    },
    {
      "first_seen": "2026-10-30T12:21:44Z",
      "native_id": "PMC:PMC13705439",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705439"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Pancreatitis Pathology and Treatment",
      "subfield": "surgery"
    }
  ],
  "title": "Integrated Single-Cell and Transcriptomic Analysis Suggests a Cuproptosis-Related Phenotype and Potential Therapeutic Target in Acute Pancreatitis",
  "title_text": "Integrated Single-Cell and Transcriptomic Analysis Suggests a Cuproptosis-Related Phenotype and Potential Therapeutic Target in Acute Pancreatitis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/3z6w06pgpdfse",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}